Chemistry Core

化学核心

• 批准号: 10592384
• 负责人: TIMOTHY S BUGNI
• 金额: $ 103.58万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592384
• 关键词: Chemistry; Core

Project Summary The ability of microbes, especially bacteria, to produce biologically active molecules that can form the basis of therapeutic agents to confront important human pathogens forms the overall premise of this CETR application. The microbial producers will be symbiotic bacteria from a variety of niches. The assays that will lead to the discovery of potential therapeutic agents will focus on multidrug resistant Gram-negative bacteria and systemic fungal pathogens. The Chemistry Core will be responsible for converting the activity discovered in biological assays into purified active molecules with known structures in sufficient amounts that secondary functional assays, structure-activity studies, and target identification can be addressed. This overall goal will be accomplished with four tasks, which are described in much greater detail in a later section of the proposal. Task 1: Produce symbiotic microbe metabolite fractions for dereplication and in vitro efficacy and safety testing. Task 2: Scale-production of promising fraction for in vivo testing and structural elucidation. Task 3: Purify and structurally characterize the active molecule/s. Task 4: Large-scale production for advanced in vivo PK/PD and mechanism of action determination.

项目概要 微生物，特别是细菌，产生生物活性分子的能力，这些分子可以构成 对抗重要人类病原体的治疗药物构成了此 CETR 应用的总体前提。 微生物生产者将是来自各种生态位的共生细菌。这些分析将导致 潜在治疗药物的发现将集中于多重耐药革兰氏阴性菌和全身性细菌 真菌病原体。化学核心将负责转化生物中发现的活性 对具有已知结构的纯化活性分子进行足够量的分析，以保证二级功能 可以解决分析、结构活性研究和靶点识别问题。这个总体目标将是 通过四项任务完成，这些任务将在提案的后面部分进行更详细的描述。 任务 1：生产共生微生物代谢物组分，用于重复复制以及体外功效和安全性 测试。 任务 2：规模化生产有前景的组分，用于体内测试和结构阐明。 任务 3：纯化活性分子并对其结构进行表征。 任务4：大规模生产先进的体内PK/PD和作用机制测定。